Discordance Between HbA1c and Glucose Management Indicator in People With Type 2 Diabetes Treated With SGLT2 Inhibitors

Abstract

Background:

The hemoglobin glycation index (HGI), defined as the difference between HbA1c and the glucose management indicator (GMI) derived from continuous glucose monitoring (CGM), has emerged as a tool to evaluate discordance between laboratory and sensor-based measures. The impact of sodium–glucose cotransporter 2 inhibitors (SGLT2i) on these markers remains unclear.

Methods:

We retrospectively analyzed CGM data from 143 individuals with type 2 diabetes, stratified by SGLT2i use. Both HGI and glycated albumin-to-HbA1c (GA/HbA1c) ratio were compared. A restricted dataset (n = 117) excluding individuals with anemia or advanced renal dysfunction was also examined.

Results:

SGLT2i users exhibited higher hematologic parameters and significantly greater HGI (full dataset: 0.3 vs 0.1, P = .0297; restricted: 0.4 vs 0.1, P = .0206), whereas the GA/HbA1c ratio was significantly lower (full: 2.27 vs 2.54, P = .0117; restricted: 2.18 vs 2.38, P = .0178). The HbA1c–GMI relationship showed significantly different slopes between SGLT2i users and non-users, while the GA–GMI relationship was consistent across groups. Multivariate analyses identified SGLT2i use as an independent determinant of both higher HGI and lower GA/HbA1c ratio, even after adjustment for age, sex, body mass index (BMI), hemoglobin, albumin, renal function, mean glucose, and glycemic variability.

Conclusion:

SGLT2i therapy alters the interpretation of glycemic markers by elevating HGI and lowering GA/HbA1c, independent of hematologic and renal factors. These findings emphasize the need for individualized assessment of glycemic control using CGM-derived metrics and complementary biomarkers.